JPH0633248B2 - Method for producing 2-alkene-5-olides - Google Patents

Description

TECHNICAL FIELD The present invention relates to a novel method for producing 2-alkene-5-olides useful as a flavoring compound having butter or milk-like aroma.

More specifically, the present invention provides a compound represented by the following formula (3) which has not been described in the prior art and can be easily synthesized from 4-hydroxy-1-alkene. However, in the formula, R represents an alkyl group, and 4-hydroxy-1,2-epoxy-alkane represented by the following formula is reacted with sodium cyanide, potassium cyanide or hydrogen cyanide to obtain the following formula (2): However, in the formula, R has the same meaning as described above to form a 3,5-dihidroxy-alkylnitrile. Next, the compound of the formula (2) is reacted by heating in the presence of an acid to give a compound of the following formula (1) However, in the formula, R has the same meaning as described above, and relates to a process for synthesizing a 2-alkene-5-olide represented by:

(Prior Art) With respect to a conventional method for producing a 2-alkene-5-olide represented by the above formula (1), for example, a synthetic method (4-methyl-2-decen-5-ol-1) shown in the following reaction process diagram is shown. -Synthetic example of carboxylic acid lactone) is known (Japanese Patent Publication No. 4)
6-41183).

According to the method shown in the above reaction process diagram, acetaldehyde and sodium acetylide were reacted in liquid ammonia to obtain the corresponding formula (7) 1-in-3-ol, which was obtained by brominating it with phosphorus tribromide. The compound of the formula (6) and hexanal are subjected to a reformatsky reaction to form an alcohol compound of the formula (5), and ethylmagnesium bromide is allowed to act on the alcohol compound to give a Grignard reagent, and then dry ice (carbon dioxide gas) is applied in the autoclave. Then, one carbon chain is extended to form a carboxylic acid, which is partially reduced using a Lindlar catalyst, and is lactonized while being distilled to obtain the target compound formula (1).

(Problems to be Solved by the Invention) As the problems in the above-mentioned method proposed in the related art, for example,
The number of steps is very long and the reaction means is extremely complicated,
In addition, in each stage, by-products are easily generated and the respective compounds cannot be obtained in high purity. Further, for example, 2-methyl-2
The total yield of -decen-5-ol-1-carboxylic acid lactone is 2.4%, which is a very low yield.

(Means for Solving Problems) The present inventors have conducted earnest research to avoid the above disadvantages or drawbacks.

As a result, 4-hydroxy-1- which can be easily synthesized in one step from alkanal which is inexpensive and easily available on the market.
It was discovered that the target compound can be industrially synthesized by using alkene as a raw material, with a short number of steps, high purity and simple operation without accompanying byproducts.

That is, the present invention provides the following formula (4) However, in the formula, R represents an alkyl group, and a 4-hydroxy-1-alkene represented by the following formula is reacted with an epoxidizing agent to obtain the following formula (3): However, in the formula, R is the same as defined above, 4-hydroxy 1,2-epoxy alkane represented by the following formula is formed, and the compound of formula (3) is reacted with sodium cyanide, potassium cyanide or hydrogen cyanide to obtain ) However, in the formula, R has the same meaning as described above to form a 3,5-dihydroxy-alkyl nitrile represented by the following formula. Then, by reacting the compound (2) with heating in the presence of an acid, the following formula (1) However, in the formula, R has the same meaning as described above, and it has been discovered that 2-alkene-5-olide represented by the following formula can be industrially produced with high purity and at low cost by a simple operation.

Therefore, an object of the present invention is to provide a method that can be easily synthesized with high purity at a low cost and industrially without accompanying byproducts, as compared with the above-mentioned conventionally proposed methods.

The production of the compound of the above formula (1) of the present invention can be represented as follows when the above embodiment including the production example of the compound of the above formula (4) is shown in a process chart.

The method for producing a 2-alkene-olide of the present invention will be described in detail below with reference to the above process chart.

The starting 4-hydroxy-1-alkene of the above formula (4) is commercially available, for example, by reacting the alkanal formula (5) with allylmagnesium chloride or allylmagnesium bromide. Can also be easily synthesized (see the reference example below).

In order to synthesize the above formula (3) from the above formula (4) 4-hydroxy-1-alkene, the compound of the formula (4) in an organic solvent,
For example, it can be easily synthesized by reacting with an epoxidizing agent in the presence of sodium acetate or sodium carbonate.

In the compound of the above formula (4) used herein, specific examples of the preferable alkyl group for R include C1 to C16 alkyl.

The reaction is, for example, about 5 ° to about 80 ° C, more preferably 1
It can be performed in the range of about 0 ° to about 50 ° C, for example, about 2 to about 50 hours, more preferably about 5 to about 30 hours.

Specific examples of the epoxidizing agent used in this reaction include peracetic acid, formic acid, perbenzoic acid, and perphthalic acid. The amount of these epoxidizing agents to be used is, for example, in the range of about 1 to about 3 mol, more preferably about 1.
The range of 1 to about 1.5 mol can be mentioned.
Examples of the organic solvent include dichloromethane, chloroform, carbon tetrachloride, dichloroethane, benzene, toluene, ether, ethyl acetate and the like. The amount of these organic solvents used is not particularly limited and can be appropriately selected. For example, a range of about 0.5 to about 10 times the weight of the compound of the formula (4) can be preferably exemplified. .

After completion of the reaction, the compound of the formula (3) can be obtained in high purity after washing with water and concentration according to a conventional method and, if necessary, purification by means such as distillation.

In the compound of the above formula (3) which can be obtained here, specific examples of the preferable alkyl group of R include, for example, C1-C16.
Can be exemplified by alkyl.

For example, in order to synthesize the 2,4-dihydroxy-alkylnitrile of the above formula (2) from the compound of the formula (3) which can be obtained as described above, for example, the compound of the formula (3) is sodium cyanide, potassium cyanide or It can be easily synthesized by reacting with hydrogen cyanide. This reaction is usually carried out with water, ethanol, methanol, C
It is carried out in the presence or absence of a solvent such as MF and an acid such as acetic acid, propionic acid, magnesium sulfate or ammonium chloride.

The reaction temperature and reaction time of the above reaction can be appropriately selected and carried out, for example, a temperature in the range of about 5 ° to about 100 ° C and a reaction time in the range of about 4 to 10 hours are preferred. It can be illustrated. The amount of sodium cyanide, potassium cyanide, or hydrogen cyanide used in this reaction is preferably about 1 to about 5 mol per 1 mol of the compound of the formula (3). The amount of the solvent used as described above is not particularly limited and may be appropriately selected.
It is used in the range of about 1 to about 20 times the weight of the compound. The amount of the above-mentioned acid to be used can also be appropriately selected, and for example, a range of about 0.5 to about 3 times the molar amount of sodium cyanide, potassium cyanide or hydrogen cyanide can be preferably exemplified. .

After completion of the reaction, put an organic solvent in the reaction product for extraction,
The compound of formula (2) can be easily obtained by washing with water and concentrating.

In the compound of the above formula (2) which can be obtained here, specific examples of the preferable alkyl group of R include, for example, C1 to C.
The alkyl of 15 can be illustrated.

Next, the formula (2) 2,4-dihydroxy-obtained above is obtained.
In order to synthesize the formula (1) 2-alkene-5-olide from an alkyl nitrile, it can be easily synthesized, for example, by reacting the compound of the formula (1) with heating in the presence of an acid.

The reaction can be carried out in a wide range of, for example, about 30 ° to about 150 ° C, more preferably about 50 ° to about 100 ° C. The reaction time can be, for example, about 0.5 to about 5 hours. Examples of the acid used in this reaction include acids such as hydrochloric acid, sulfuric acid and phosphoric acid. The amount of these acids used is not particularly limited and may be appropriately selected. For example, the amount used is preferably about 0.2 to about 5 mol times with respect to the compound of the formula (2).

After completion of the reaction, an organic solvent is injected into the reaction product for extraction. The extract can be washed with a saline solution, then with an alkaline solution, and concentrated to obtain the target compound formula (1). The obtained compound of formula (1) can be purified by a means such as distillation, if necessary.

Thus, specific examples of the compound of formula (1) that can be synthesized in the present invention include, for example, 2-hexene-5-olide, 2-heptene-5-olide, 2-octene-5-olide, and 2-nonene. -5-Olido, 2-decene-5-olid, 2-undecene-5-olid, 2-dodecene-5-
Olide, 2-tridecene-5-olide, 2-tetradecene-5-olide, 2-ventadecene-5-olide, 2-
Preferred examples include hexadecene-5-olide, 2-pentadecene-5-olide, 2-heptadecene-5-olide, 2-octadecene-5-olide, 2-nonadecene-5-olide and 2-eicosane-5-olide. be able to.

Hereinafter, embodiments of the present invention will be described in more detail with reference to examples.

Reference Example (1) Synthesis of 4-hydroxy-1-nonene formula (4).

Magnesium 26.4g in a flask, ether 200m
1 was charged, and a mixed solution of 80.3 g of allyl chloride and 400 ml of ether was added dropwise thereto over 2.5 hours.
After dropping, stir at 25 ° C for 40 minutes and then add hexanal 100g.
(0.1 mol) was added dropwise at 5 ° to 10 ° C over 2 hours,
After completion of the stirring, the mixture was stirred at 10 ° to 15 ° C for 2 hours, poured into a saturated ammonium aqueous solution, the ether layer was washed with a saline solution, dried, concentrated and distilled under reduced pressure to obtain 120.6 g of the target compound ( Yield: 84.6%). Boiling point; 48
° -50 ° C / 2mmHg.

(2) Various 4-hydroxy-1-alkenes were synthesized according to Reference Example (1). The results are shown in Table-1.

EXAMPLES (1) Synthesis of 4-hydroxy-1,2-epoxy-nonane formula (3).

14.2 g of 4-hydroxy-1-nonene in the flask
(0.1 mol), 1 g of sodium acetate and 150 ml of dichloromethane were charged, and 40% peracetic acid was added dropwise thereto at 20 ° to 23 ° C over 1 hour. Stir at room temperature for 10 hours after dropping. The reaction solution was washed successively with water and ferrous sulfate aqueous solution, dried, concentrated and distilled under reduced pressure to obtain 14.2 g of the compound of formula (3) (yield: 88.6%). It was

(2) Various 4-hydroxy-1,2-epoxy-1-
The alkene was synthesized according to Example (1). The results are shown in Table-2.

(3) Synthesis of 2,4-hydroxy-nonyl nitrile formula (2).

A flask was charged with 30 ml of water, 50 ml of 95% ethanol and 4.78 g of potassium cyanide, to which 4-hydroxy-1,2-epoxynonane was added dropwise at 10 ° C over 1 hour. At this time, 4.41 g of acetic acid was injected at the same time. After completion of dropping, after stirring at room temperature for 10 hours,
Heat at 70 ° -80 ° C for hours and cool. The reaction product is extracted with dichloromethane, washed with water, dried and concentrated. After concentration, distill under reduced pressure, boiling point 165 ° C-168 ° C / 2
11.5 g of the title compound with mmHg were obtained.

(4) Various 2,4-hydroxy-alkyl nitrile formulas (2) were synthesized according to Example (3). The results are shown in Table-3.

(5) Synthesis of 2-decene-5-olido formula (1).

2,4 dihydroxy-nonylniotril 7.
9 g (0.043 mol), concentrated hydrochloric acid 5 g (0.05 mol)
And stir at 80 ° C for 2 hours. Then, the reaction solution is cooled and extracted with toluene. The toluene layer is washed with brine, then with an aqueous alkaline solution, and then concentrated. Distillation under reduced pressure gave 5.81 of the title compound having a boiling point of 107 ° -111 ° C / 2 mmHg (yield; 80.5
%).

(6) Various 2-alkene-5-olides Formula (1) was synthesized according to Example (5). The results are shown in Table-4.

(Effect of the Invention) According to the present invention, it is possible to provide a method capable of industrially inexpensively and easily producing 2-alkene-5-olides useful as a flavoring substance having a buttery or milky odor.

That is, 4-hydroxy-1- which can be easily synthesized in one step from alkanal which is inexpensive and easily available on the market.
Provide a method of synthesizing an objective compound in a high yield industrially with an alkene as a raw material, with a reduced number of steps compared to conventional production methods, with high purity and a simple operation without accompanying byproducts. be able to.

Claims (2)

[Claims] 1. The following formula (2) In the formula, R represents an alkyl group, and the 3,5-dihydroxy-alkyl nitrile represented by the formula (1) is characterized by reacting by heating in the presence of an acid. In the formula, R represents an alkyl group, and a method for producing a 2-alkene-5-olide represented by the formula: 2. The following formula (4) In the formula, R represents an alkyl group, and 4-hydroxy-1-alkene represented by the following formula is reacted with an epoxidizing agent to obtain the following formula (3): In the formula, R has the same meaning as described above, 4-hydroxy-1,2-epoxyalkane represented by the following formula is formed, and the obtained compound of the formula (3) is reacted with sodium cyanide, potassium cyanide or hydrogen cyanide, Formula (2) In the formula, R represents an alkyl group, and a 3,5-dihydroxy-alkyl nitrile represented by the following formula is formed, and the compound of the formula (2) is then reacted by heating in the presence of an acid. 1) In the formula, R represents an alkyl group, and a method for producing a 2-alkene-5-olide represented by the formula: